If you really have a question this post just goes to show that alot of reading can lead to some solid knowledge.
Alpha Lipoic Acid
A lipid and water soluble antioxidant, the pure R(+) enantiomer of which is produced in minute quantities by the body.
Below we present a summary of the major research results for alpha lipoic acid (aLA) taken from published scientific studies. We give evidence that most of these highly beneficial effects derived from the R(+) enantiomer (RLA). We show why this is particularly true for the benefits of aLA with respect to mitochondria, which benefits are almost certainly the most important for life extensionist purposes. We also present studies of the properties of the S(-) enantiomer (synthesized only by man) and of the racemate (50/50 mixture of R & S - RSLA). Finally, we present evidence of the relative merits of the different forms of aLA which are available (ie pure R(+) and racemate).
Safety, Interactions and Pharmacology
10 patients with diabetic neuropathy were given 70 days of treatment with a single dose of 600 mg of alpha lipoic acid [RSLA] per dayR.
"Seventy-four patients with type-2 diabetes were randomized to either placebo (n = 19); or active treatment for 4 weeks in various doses of 600 mg once daily (n = 19), twice daily (1200 mg; n = 18), or thrice daily (1800 mg; n = 18) alpha-lipoic acid [RSLA]."R
"the chronic administration of lipoic acid reduces the activities of biotin-dependent pyruvate carboxylase and beta-methylcrotonyl-CoA carboxylase; enzyme activities remain normal if biotin at pharmacological doses is administered together with lipoic acid. Even without supplemental biotin, the decreases in enzyme activities are not dramatic and would presumably not cause pathology in patients."R
However, this last conclusion is likely made for moderate doses of aLA and biotin is so importantR that it should probably be supplemented for dosages of aLA above 50 mg daily.
In a study of iv and oral dosage of RSLA in 12 healthy volunteers, the area under the curve of serum concentration for 200 mg iv and 600 mg oral was 3.4 times that for 200 mg oral. The half-life (in the range of 25.3-32.7 min) was not significantly different between dosage amounts and types. Note that this serum half-life does not necessarily imply that RSLA is of no value to the body after a few half lives since is may have simply left the blood to enter the cells to provide benefits there.R
In a trial of 39 NIDDM patients with cardiac autonomic neuropathy (CAN), treatment with RSLA using a well-tolerated oral dose of 800 mg/day for 4 months slightly improved CAN.R
Proven Benefits of aLA, RSLA and RLA
" feeding old rats ALCAR and/or [RLA] improved performance on memory tasks, reduced brain mitochondrial structure decay, and reduced oxidative damage in the brain. The combination of ALCAR and [RLA] showed a greater effect than ALCAR or [RLA] alone. These results suggest that feeding a combination of mitochondrial metabolites to old animals may prevent mitochondrial decay in neurons and restore cognitive dysfunction. These results also suggest that consumption of high levels of mitochondrial metabolites may be an efficient intervention in humans for delaying brain aging and age-associated neurodegenerative diseases"R.
"feeding old rats high levels of key mitochondrial metabolites [RLA and ALCAR] can ameliorate oxidative damage, enzyme activity, substrate-binding affinity, and mitochondrial dysfunction"R.
"ALCAR+[RLA] partially reversed the age-related decline in average mitochondrial membrane potential and significantly increased hepatocellular O2 consumption, indicating that mitochondrial-supported cellular metabolism was markedly improved by this feeding regimen. ALCAR+[RLA] also increased ambulatory activity in both young and old rats; moreover, the improvement was significantly greater in old versus young animals and also greater when compared with old rats fed ALCAR or [RLA] alone"R.
In an investigation of "the role of the thiol antioxidant dihydrolipoic acid (DHLA) and intracellular glutathione (GSH) in RLA-stimulated glucose transport" and an exploration of "the hypothesis that RLA could increase glucose uptake into 3T3-L1 adipocytes in an oxidant-mimetic manner"R, the following was found:
"3T3-L1 adipocytes have a low capacity to reduce R-LA and the oxidized form of lipoic acid is responsible for stimulating glucose uptake,
R-LA modulates glucose uptake by changing the intracellular redox status, and
the insulin receptor is a potential cellular target for R-LA action."
In obese Zucker rats, RLA (30 mg/kg body weight by ip injection once daily) and exercise training "interact in an additive fashion to improve insulin action in insulin-resistant skeletal muscle"R. However, in insulin-sensitive lean Zucker rats, "the beneficial interactive effects of exercise training and RLA on skeletal muscle insulin action --- are not apparent"R. An important observation of the study of lean rats was that chronic supplementation with RLA was associated with a significantly reduced rate of body weight gain of fat mass. In both studies, RLA supplementation reduced the levels of protein carbonyls (an indicator of long-term oxidative damage). Another important finding was that use of RLA without exercise caused a significant increase in serum free fatty acid levels.
"600 mg [RLA] was given daily to nine patients with AD and related dementias (receiving a standard treatment with acetylcholinesterase inhibitors) in an open study over an observation period of, on average, 337+/-80 days. The treatment led to a stabilization of cognitive functions in the study group ... Despite the fact that this study was small and not randomized, this is the first indication that treatment with [RLA] might be a successful 'neuroprotective' therapy option for AD and related dementias."R
"When cultured rat L6 muscle cells were exposed to glucose oxidase and glucose to generate H2O2 and cause oxidative stress, there was a marked decrease in insulin-stimulated glucose transport. Pretreatment with LA over the concentration range of 10-1,000 pmol/l protected the insulin effect from inhibition by H2O2. Both the R and S isomers of LA were equally effective. In addition, oxidative stress caused a significant decrease (approximately 50%) in reduced glutathione concentration, along with the rapid activation of the stress-sensitive p38 mitogen-activated protein kinase. Pretreatment with LA prevented both of these events, coincident with protecting insulin action. These studies indicate that in muscle, the major site of insulin-stimulated glucose disposal, one important effect of LA on the insulin-signaling cascade is to protect cells from oxidative stress-induced insulin resistance."R
In a study in which "some rats were ... supplemented with 0.2% (w/w) [RLA] for 2 wk prior to death"R, the following statements were made and results found:
RLA "increases or maintains levels of other low molecular weight antioxidants such as ubiquinone, glutathione (GSH), and ascorbic acid."
"Overall, our results show that the aging rat myocardium exhibits increased oxidant production, significantly lower ascorbic acid levels, and a marked increase in steady-state levels of oxidative DNA damage. [RLA] supplementation significantly reverses the age-related decline in myocardial ascorbic acid content, and lowers the rate of oxidant production and the steady-state levels of oxidative DNA damage. Our results thus indicate that dietary supplementation with lipoic acid may be an effective means to lower increased myocardial oxidative stress with age."
"Thus, in addition to its antioxidant effect, dihydrolipoic acid [reduced RLA] may protect against lipid peroxidation by chelating free metal ions in vivo."
"Our present findings suggest that [RLA] supplementation may be a safe and effective means of improving systemic decline in over all metabolic function and also increase protection against both endogenous and external production of ROS."
"However, long-term feeding studies with [RLA] are needed to determine whether benefits of [RLA] seen in old animals can be sustained over time."
"Dietary supplementation of rats with (R)-lipoic acid [0.5% (wt/wt)] for 2 weeks completely reversed the age-related decline in hepatocellular GSH levels and the decreased (with age) lethal dosage of tert-butylhydroperoxide (t-BuOOH)to hepatocytes. An identical supplemental diet fed to young rats did not enhance the resistance of hepatocytes to t-BuOOH, indicating that antioxidant protection was already optimal in young rats. Thus, this study shows that cells from old animals are more susceptible to oxidant insult and (R)-lipoic acid, after reduction to an antioxidant in the mitochondria, effectively reverses this age-related increase in oxidant vulnerability."R
In an in vivo study of ischaemia-reperfusion (I-R) of rats, a 14 week supplementation of 10,000 IU vitamin E/kg and 1.65 g alpha-LA/kg of diet did not influence cardiac performance or the incidence of dysrhythmias, even though it did decrease lipid peroxidation during I-R in young (4 months) adult ratsR. However, in a concurrent experiment with old (18 months) adult rats, the same supplemental regimen was found to protect the aged rat heart from I-R-induced lipid peroxidation by scavenging numerous reactive oxygen species, and this protection was associated with improved cardiac performance during reperfusionR.
In a randomized clinical trial, "a total of 31 healthy adults were supplemented for 2 months either with alpha lipoic acid (LA) (600 mg/d, n = 16), or with alpha tocopherol (AT) (400 IU/d, n = 15) alone, and then with the combination of both for 2 additional months. LA significantly increased the lag time of LDL lipid peroxide formation for both copper-catalyzed and AAPH-induced LDL oxidation, decreased urinary F2-isoprostanes levels, and plasma carbonyl levels after AAPH oxidation. AT prolonged LDL lag time of lipid peroxide formation and conjugated dienes after copper-catalyzed LDL oxidation, decreased urinary F2-isoprostanes, but had no effect on plasma carbonyls. The addition of LA to AT did not produce an additional significant improvement in the measures of oxidative stress. In conclusion, LA supplementation functions as an antioxidant, because it decreases plasma- and LDL-oxidation and urinary isoprostanes"R.
"This placebo-controlled explorative study confirms previous observations of an increase of insulin sensitivity in type-2 diabetes after acute and chronic intravenous administration of ALA. The results suggest that oral administration of alpha-lipoic acid can improve insulin sensitivity in patients with type-2 diabetes"R.
"We also observed that the insulin-mimetic nutrient alpha-lipoic acid (LA; R-enantiomer) is able to stimulate glucose uptake in cytokine-treated cells that are insulin resistant. This study shows that cytokine-induced glucose uptake in skeletal muscle cells is redox sensitive and that, under conditions of acute infection that is accompanied with insulin resistance, LA may have therapeutic implications in restoring glucose availability in tissues such as the skeletal muscle."R
"When a diet supplemented with RLA (0.5% w/w), a mitochondrial coenzyme, was fed to old rats to determine its efficacy in reversing the decline in metabolism seen with age for 2 wk, hepatocytes from untreated old rats vs. young controls had significantly lower oxygen consumption and mitochondrial membrane potential, whereas supplementation reversed the age-related decline in O2 consumption and increased mitochondrial membrane potential in old rats. Ambulatory activity, a measure of general metabolic activity, was almost threefold lower in untreated old rats vs. controls, but this decline was reversed in old treated rats. Malondialdehyde (MDA) levels, an indicator of lipid peroxidation, were increased fivefold with age in cells from unsupplemented rats, whereas supplementation reduced MDA levels markedly. Both glutathione and ascorbic acid levels declined in hepatocytes with age, but their loss was completely reversed with RLA acid supplementation. Thus, RLA supplementation improves indices of metabolic activity as well as lowers oxidative stress and damage evident in aging"R.
"A two-week dietary supplementation of old animals with 0.5% RLA acid prior to cell isolation almost completely reversed the age-associated effects on ascorbic acid concentration, recycling and biosynthesis after oxidative stress"R.
The chelating power of LA against copper is due solely to its reduced form, DHLA. "in our LDL experiments at physiological pH, DHLA [but not LA] is able to either reductively inactivate Cu2+ when Cu2+ is in excess, or effectively chelate Cu2+ when DHLA is in excess. The Cu2+
HLA complex [which is stable at low pH or in the absence of oxygen] eventually undergoes copper-catalyzed oxidation, copper is released and LDL peroxidation proceeds. DHLA, thus, has both pro- and antioxidant properties depending upon the ratio of Cu2+
HLA and the pH. These results provide an additional mechanism of thiol-mediated formation of radicals and metal chelation."R
"In diabetic rats, after 6 weeks of diabetes, 2 weeks of racLPA treatment corrected 20% sciatic motor and 14% saphenous sensory NCV deficits. The ED50 for motor nerve conduction velocity (NCV) restoration was approximately 38 mg kg(-1) day(-1). aLA also corrected a 49% diabetic deficit in sciatic endoneurial blood flow. R and S-LA enantiomers were equipotent in correcting NCV and blood flow deficits. Treatment of diabetic rats with low doses (20 mg kg(-1) day(-1)) of aLA and gamma linolenic acid (GLA), while having modest effects on their own, showed evidence of marked synergistic action in joint treatment, completely correcting motor NCV and blood flow deficits."R
"In the Alpha-Lipoic Acid in Diabetic Neuropathy Study, 328 patients with NIDDM and symptomatic peripheral neuropathy were randomly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses (ALA 1,200 mg; 600 mg; 100 mg) or placebo (PLAC) over 3 weeks. The total symptom score (TSS) (pain, burning, paresthesia, and numbness) in the feet decreased significantly from baseline to day 19 in ALA 1,200 and ALA 600 vs. PLAC. Each of the four individual symptom scores was significantly lower in ALA 600 than in PLAC after 19 days. The total scale of the Hamburg Pain Adjective List (HPAL) was significantly reduced in ALA 1,200 and ALA 600 compared with PLAC after 19 days. In the Deutsche Kardiale Autonome Neuropathie Studie, patients with NIDDM and cardiac autonomic neuropathy diagnosed by reduced heart rate variability were randomly assigned to treatment with a daily oral dose of 800 mg alpha-lipoic acid (ALA) (n = 39) or placebo (n = 34) for 4 months. Two out of four parameters of heart rate variability at rest were significantly improved in ALA compared with placebo. A trend toward a favorable effect of ALA was noted for the remaining two indexes. In both studies, no significant adverse events were observed. In conclusion, intravenous treatment with alpha-lipoic acid (600 mg/day) over 3 weeks is safe and effective in reducing symptoms of diabetic peripheral neuropathy, and oral treatment with 800 mg/day for 4 months may improve cardiac autonomic dysfunction in NIDDM"R.
In a group of 14 immunosuppressed NMRI-mice (nu/nu) raised and kept under germ-reduced conditions, RLA "(9 mg/kg body weight) expanded the total life span of its group."R
"In L6 muscle cells and 3T3-L1 adipocytes in culture, glucose uptake was rapidly increased by (R)-thioctic acid. The increment was higher than that elicited by the (S)-isomer or the racemic mixture and was comparable with that caused by insulin... Thioctic acid provoked an upward shift of the glucose-uptake insulin dose-response curve. The molar content of GLUT1 and GLUT4 transporters was measured in both cell lines. 3T3-L1 adipocytes were shown to have >10 times more glucose transporters but similar ratios of GLUT4:GLUT1 than L6 myotubes. The effect of (R)-thioctic acid on glucose transporters was studied in the L6 myotubes. Its stimulatory effect on glucose uptake was associated with an intracellular redistribution of GLUT1 and GLUT4 glucose transporters, similar to that caused by insulin, with minimal effects on GLUT3 transporters. In conclusion, thioctic acid stimulates basal glucose transport and has a positive effect on insulin-stimulated glucose uptake. The stimulatory effect is dependent on phosphatidylinositol 3-kinase activity and may be explained by a redistribution of glucose transporters. This is evidence that a physiologically relevant compound can stimulate glucose transport via the insulin signaling pathway."R
"Using an in vitro lipid peroxidation model with an ascorbate-iron-EDTA system and an incubation medium containing 20 mM glucose which increased lipid peroxidation up to fourfold, a dose-dependent and statistically significant reduction in lipid peroxidation was seen in rat brain and sciatic nerve with similar potencies for both enantiomers and the racemate of alpha-lipoic acid. This effect was unassociated with any reduction in the loss of alpha-tocopherol."R
RLA "improved longer-term memory of aged female NMRI mice in the habituation in the open field test at a dose of 100 mg/kg body weight for 15 days."R
Potential Benefits
RLA "supplementation may increase cellular and mitochondrial antioxidant status, thereby effectively attenuating any putative increase in oxidative stress with age"R.
Negative Results and Limitations
"For 6 wk, lean Zucker rats either remained sedentary, received R-ALA (30 mg. kg body wt(-1). day(-1)), performed exercise training (ET - treadmill running), or underwent both R-ALA treatment and ET. ET alone or in combination with R-ALA significantly increased (P < 0.05) peak oxygen consumption (28-31%) and maximum run time (52-63%). During an oral glucose tolerance test, ET alone or in combination with R-ALA resulted in a significant lowering of the glucose response (17-36%) at 15 min relative to R-ALA alone and of the insulin response (19-36%) at 15 min compared with sedentary controls. Insulin-mediated glucose transport activity was increased by ET alone in isolated epitrochlearis (30%) and soleus (50%) muscles, and this was associated with increased GLUT-4 protein levels. Insulin action was not improved by R-ALA alone, and ET-associated improvements in these variables were not further enhanced with combined ET and R-ALA. Although ET and R-ALA caused reductions in soleus protein carbonyls (an index of oxidative stress), these alterations were not significantly correlated with insulin-mediated soleus glucose transport. These results indicate that the beneficial interactive effects of ET and R-ALA on skeletal muscle insulin action observed previously in insulin-resistant obese Zucker rats are not apparent in insulin-sensitive lean Zucker rats."R
"we only observed a beneficial effect of [RLA] only in old and not in young animals."R
"The decline observed in the plasma concentration was steep (t1/2, 0.5 h)"R. ie RLA or RSLA have short plasma half-lives.
RLA did not improve "longer-term memory ... in the habituation in the open field test at a dose of 100 mg/kg body weight for 15 days ... for young mice"R.
Nill Value, Different, or Negative Results for the S enantiomer
"These findings indicate that (i) the activities of the mammalian pyruvate dehydrogenase complex and its catalytic components are affected by lipoic compounds based on their stereoselectivity; and (ii) the oxidation of pyruvate by intact HepG2 cells is not inhibited by R-LA by is moderately decreased by S-LA. The later finding with the intact cells is in support of therapeutic role of R-LA as an antioxidant" and the reduced value of S-LA.R
"Maximum plasma concentrations (Cmax) of the R-(+)-enantiomer were about 40-50% higher than those of the S-(-)-enantiomer (50 mg: 135.45 ng/ml R-(+)-TA, 67.83 ng/ml S-(-)-TA; 600 mg: 1812.32 ng/ml R-(+)-TA, 978.20 ng/ml S-(-)-TA; geometric means)."R
"The concentrations of glutathione in normal lenses or lenses incubated with R- or racemic alpha-LA were not significantly different, but the concentration of glutathione in lenses incubated with S-alpha-LA was significantly lower than the R-alpha-LA-incubated lenses."R
The individual effects of the pure R-(+) and S-(-) enantiomers of alpha-lipoic acid to enhance insulin-stimulated glucose metabolism in skeletal muscle was studied in obese Zucker rats: an animal model of insulin resistance, hyperinsulinemia, and dyslipidemia. Generally, RLA had major positive effects on all studied parameters. SLA had either no effect on all parameters except: 1) a negative chronic effect on insulin (15% increase versus 17% decrease for RLA), 2) a lesser positive chronic effect on 2-deoxyglucose uptake (65% increase by RLA versus 29% by SLA), 3) glucose transporter (GLUT-4) protein was unchanged after chronic RLA treatment but was reduced to 81 +/- 6% of obese control with SLA treatment. The study conclusion was: "the R-(+) enantiomer being much more effective than the S-(-) enantiomer."R
In a group of 14 immunosuppressed NMRI-mice (nu/nu) raised and kept under germ-reduced conditions, SLA, even at 75 mg/kg body weight per day, increased the 50% survival rate, but did not expand "the total life span of its group"R.
"An intact organ, the isolated perfused rat heart, reduced R-lipoate six to eight times more rapidly than S-lipoate ... On the other hand, erythrocytes, which lack mitochondria, somewhat more actively reduced S- than R-lipoate ... Thus, mechanisms of reduction of alpha-lipoate are highly tissue-specific and effects of exogenously supplied alpha-lipoate are determined by tissue glutathione reductase and dihydrolipoamide dehydrogenase activity"R.
"In L6 muscle cells and 3T3-L1 adipocytes in culture, glucose uptake was rapidly increased by (R)-thioctic acid. The increment was higher than that elicited by the (S)-isomer or the racemic mixture and was comparable with that caused by insulin."R
"Rat lens opacity formation and LDH leakage, resulting from incubation in medium containing 55.6 mM glucose to model diabetes, were suppressed by the addition of 1 mM R-lipoic acid. Addition of 1 mM racemic lipoic acid reduced these damaging effects to the lens by only one-half, while S-lipoic acid only potentiated LDH leakage, consistent with the hypothesis that R-lipoic acid is the active form. Although HPLC analysis demonstrated that both stereoisomers of lipoic acid were reduced to dihydrolipoate at comparable rates by the intact lens, the mitochondrial lipoamide dehydrogenase system is highly specific for reduction of exogenous R-lipoic to dihydrolipoic acid. Therefore, stereospecific protection against this opacity is consistent with specific reduction of R-lipoic acid in mitochondria of the vulnerable cells at the lens equator where the first globular degeneration is seen in glucose cataract."R
This study revealed a marked stereospecificity in the prevention of induced cataract, and in the protection of lens antioxidants, in newborn rats by alpha-lipoate, R- and racemic alpha-lipoate Cataract formation was decreased from 100% to 55% by R-alpha-lipoic acid and 40% by rac-alpha-lipoic acid. S-alpha-lipoic acid had no effect on induced cataract formation. The lens antioxidants glutathione, ascorbate, and vitamin E were depleted to 45, 62, and 23% of control levels, respectively, by the cataract inducing treatment, but were maintained at 84-97% of control levels when R-alpha-lipoic acid or rac-alpha-lipoic acid were administered; S-alpha-lipoic acid administration had no protective effect on lens antioxidants. When enantiomers of alpha-lipoic acid were administered to animals, R-alpha-lipoic acid was taken up by lens and reached concentrations 2- to 7-fold greater than those of S-alpha-lipoic acid, with rac-alpha-lipoic acid reaching levels midway between the R-isomer and racemic form. Reduced lipoic acid, dihydrolipoic acid, reached the highest levels in lens of the rac-alpha-lipoic acid-treated animals and the lowest levels in S-alpha-lipoic acid-treated animals. These results indicate that the protective effects of alpha-lipoic acid against induced cataract are probably due to its protective effects on lens antioxidants, and that the stereospecificity exhibited is due to selective uptake and reduction of R-alpha-lipoic acid by lens cellsR.
"Racemic lipoic acid is therapeutically applied in pathologies in which free radicals are involved. The in vivo reduction of lipoic acid may play an essential role in its antioxidant effect. It was found that mitochondrial lipoamide dehydrogenase reduces the R-enantiomer 28 times faster than the S-enantiomer of lipoic acid. S-lipoic acid inhibits the reduction of the R enantiomer only at relatively high concentrations."R
"Whereas mitochondrial ATP synthesis was increased when the R-enantiomer was previously added to the working rat heart at 0.05-0.1 mumol concentration, with the S-enantiomer ATP synthesis remained within the control range. Mitochondrial membrane fluidity ... revealed a trend towards increase with the R- and decrease with the S-enantiomer."R
"In feeding experiments, however, R lipoate significantly inhibited glucose oxidase-mediated skin inflammation, while S lipoate was only marginally protective."R
RLA "is the naturally occurring cofactor in alpha-ketoacid dehydrogenases. We show both photometrically by NADH+H+ oxidation and by HPLC product analysis that this enantiomer is rapidly reduced by NADH+H+ catalyzed by porcine heart lipoamide dehydrogenase/diaphorase. The racemate exhibits approximately 40% activity as compared to the form while the S(-) enantiomer photometrically shows little activity and yields no detectable reduced lipoic acid."R
The reduction of exogenous alpha-lipoic acid to dihydrolipoate by mammalian cells and tissues confers additional antioxidant protection to the cell. Both (R+) and (S-) isomers of alpha-lipoic acid were analyzed as substrates with glutathione reductase from several sources and with mammalian lipoamide dehydrogenase. Mammalian glutathione reductase catalyzed faster reduction of (S)-lipoic acid (1.4-2.4-fold greater activity) than of (R)-lipoic acid, whereas lipoamide dehydrogenase had a very marked preference for (R)-lipoic acid (18-fold greater activity) over (S)-lipoic acid"R.
"The hyperglycemic effects of D-glucose [on erythrocyte membrane fluidity] were corroborated with isolated, reconstituted membrane proteins and erythrocyte glucose carrier, indicating that, in general, the observed divergent biochemical/biophysical changes of the red cell membrane are influenced by the glucose transport protein GluT1. The natural R-form and the S-form of alpha-lipoic acid were compared with racemic R-/S-forms for their efficiencies in alterations of red cell membrane fluidity. Decreased fluidities in presence of 10 mM glucose were found to be influenced in differentiated ways: the S-form was highly active in increasing fluidity at 4 nmol/mg and increasingly less active up to 20 nmol/mg protein. By contrast the R-form of lipoic acid was moderately efficient in increasing fluidity through a larger concentration range between 4 and 80 nmol/mg protein"R.
Conclusions
The studies listed above have shown that:
SLA has effects in the body which are different than RLA.
Although SLA is an excellent antioxidant (but RLA is better) none of the other effects of SLA have been shown to be beneficial.
Since SLA does not naturally occur in the body and consequently the body has not developed mechanisms to deal with it, the effects of non-physiological doses of SLE are more likely to be harmful than are non-physiological doses of RLA which does occur naturally in the body and for which it does have mechanisms to deal with it.
Therefore, SLA should not be considered as mere filler in the racemic mixture of enantiomers which is widely available on the supplement market, but should be considered potentially harmful until proven otherwise. This not to say that non-physiological doses of RLA may not also be harmful, only that they are less likely to be so. In particularly, RLA is likely to be less harmful and more beneficial than the racemate generally used.
Additional Reading
Thiol homeostasis and supplements in physical exercise.
"Thiols are a class of organic sulfur derivatives (mercaptans) characterized by the presence of sulfhydryl residues. In biological systems, thiols have numerous functions, including a central role in coordinating the antioxidant defense network. Physical exercise may induce oxidative stress. In humans, a consistent marker of exercise-induced oxidative stress is blood glutathione oxidation. Physical training programs have specific effects on tissue glutathione metabolism that depend on the work program and the type of tissue. Experimental studies show that glutathione metabolism in several tissues sensitively responds to an exhaustive bout of exercise. Study of glutathione-deficient animals clearly indicates the central importance of having adequate tissue glutathione to protect against exercise-induced oxidative stress. Among the various thiol supplements studied, N-acetyl-L-cysteine and alpha-lipoic acid hold the most promise."R (Full text available)
Neuroprotection by the metabolic antioxidant alpha-lipoic acid.
"Very few neuropharmacological intervention strategies are currently available for the treatment of stroke and numerous other brain disorders involving free radical injury. We propose that the various metabolic antioxidant properties of alpha-lipoate relate to its possible therapeutic roles in a variety of brain and neuronal tissue pathologies: thiols are central to antioxidant defense in brain and other tissues. The most important thiol antioxidant, glutathione, cannot be directly administered, whereas alpha-lipoic acid can. In vitro, animal, and preliminary human studies indicate that alpha-lipoate may be effective in numerous neurodegenerative disorders."R
Taken from:
http://morelife.org/supplements/RLA.html
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